By the year 2015, it is estimated that 50% of HIV-1 infected persons in the US will be 50 or older. HIV-1 affects much the same cognitive processes as those altered by aging, and HIV-1-associated clinical disease progression appears more rapid in older individuals. The longitudinal data from over 20 years in the Multi- Center AIDS Cohort Study (MACS) provides an unparalleled opportunity to examine the relationship of older age to HIV-1-associated cognitive impairment. Our prior work has demonstrated associations between older age and HIV-1-associated neuropsychological performance, symptoms of minor cognitive-motor disorder, immune measures (CD4/CD8 ratio;CD8 cell percentage), and plasma viral load. The overall objective of the proposed MACS database study is to determine whether aging and HIV-1 infection have a synergistic effect on the frequency and rate of the progression of neurocognitive impairment and disorder (MCMD and HAD), pre- and post-HAART. That is, are the effects of both aging and HIV-1 infection on cognition significantly greater than the simple sum of the effects of each factor alone? We plan to create four sub-groups from the MACS sample: older (>50) and younger (18-39) HIV-1-seropositive and older and younger HIV-1-seronegative individuals. Control variables will include sociodemographic characteristics;antiretroviral medication regimen used (by CNS penetration and adherence);CDC clinical disease stage;CD4 cell nadir;depressed and anxious mood levels;alcohol and psychoactive substance use;prescribed psychotropic medication use;HIV-1- associated physical symptom burden;comorbid medical conditions;pain and fatigue levels;and global nutritional status. We also plan to examine the contribution of the presence of HIV-1-associated neurocognitive impairment and disorder to decreased functional status as well as to increased mortality rates, pre- and post-HAART. A well-controlled examination of the comprehensive and extensive longitudinal MACS study data set could generate new and clinically significant information upon which to guide future clinical interventions to address the needs of this rapidly growing group of HIV-1 infected patients today. Until the late-1990s, older age and HIV-1 infection were thought to be non-overlapping health issues. Between 1996 and 1997, newly reported AIDS cases among older persons increased by 12.6%. By the year 2015, it is estimated that 50% of HIV-1 infected persons in the US will be 50 or older. Older age at onset of AIDS is a risk factor for the occurrence of and the more rapid development of HIV-associated dementia as well as minor cognitive-motor disorder and sub-clinical neurocognitive impairment.